• Journal of Life Science
• /
• v.34 no.6
• /
• pp.418-425
• /
• 2024

Solid tumors are heterogeneous populations of multiple cell types. While the majority of the cells that comprise cancer are unable to divide, cancer stem cells have self-renewal and differentiation properties. Normal stem cell pathways that control self-renewal are overactivated in cancer stem cells, making cancer stem cells important for cancer cell expansion and progression. Dick first proposed the definition of cancer stem cells in acute myeloid leukemia, according to which cancer stem cells can be classified based on the expression of cell surface markers. Cancer stem cells maintain their potential in the tumor microenvironment. Multiple cell types in the tumor microenvironment maintain quiescent cancer stem cells and serve as regulators of cancer growth. Since current cancer treatments target proliferative cells, quiescent state cancer stem cells that are resistant to treatment increase the risk of recurrence or metastasis. Various signals of the tumor microenvironment induce changes to become a tumor-supportive environment by remodeling the vasculature and extracellular matrix. To effectively treat cancer, cancer stem cells and the tumor microenvironment must be targeted. Therefore, it is important to understand how the tumor microenvironment induces reprogramming of the immune response to promote cancer growth, immune resistance, and metastasis. In this review, we discuss the cellular and molecular mechanisms that can enhance immunosuppression in the tumor microenvironment.

• Journal of Internet Computing and Services
• /
• v.21 no.2
• /
• pp.19-26
• /
• 2020

This paper analyses the feasibility of using implantable antennas to detect and monitor tumors. We analyze this setting according to the wireless propagation loss and signal fading produced by human bodies and their environment in an indoor scenario. The study is based on the ITU-R propagation recommendations and prediction models for the planning of indoor radio communication systems and radio local area networks in the frequency range of 300 MHz to 100 GHz. We conduct primary estimations on 915 MHz and 2.4 GHz operating frequencies. The path loss presented in most short-range wireless implant devices does not take into account the human body as a channel itself, which causes additional losses to wireless designs. In this paper, we examine the propagation through the human body, including losses taken from bones, muscles, fat, and clothes, which results in a more accurate characterization and estimation of the channel. The results obtained from our simulation indicates a variation of the return loss of the spiral antenna when a tumor is located near the implant. This knowledge can be applied in medical detection, and monitoring of early tumors, by analyzing the electromagnetic field behavior of the implant. The tumor was modeled under CST Microwave Studio, using Wisconsin Diagnosis Breast Cancer Dataset. Features like the radius, texture, perimeter, area, and smoothness of the tumor are included along with their label data to determine whether the external shape has malignant or benign physiognomies. An explanation of the feasibility of the system deployment and technical recommendations to avoid interference is also described.

• Fisheries and Aquatic Sciences
• /
• v.9 no.3
• /
• pp.107-114
• /
• 2006

A dermal sarcoma was found in a freshwater, soft-shelled turtle Pelodiscus sinensis. The neoplasm consisted of proliferating fibrous tissue and extended from the dermis. The overlying epidermis was hyperplastic and partially folded. The deeper dermis and hypodermis contained three large, discrete necrotic foci of -10 mm diameter. Numerous eosinophilic granule cells and macro phages surrounded the necrotic areas. A mixed population of cells with nuclear pleomorphism was observed between the papillary layers of vessels. This area also had regions of different histological structures: (l) regularly arranged, spindle-shaped cells with compact nuclei in a fine-fibrillar matrix; (2) haphazardly arranged cells ($\leq$ 23 11m diameter) with ovoid, highly hypertrophic, faintly stained nuclei; and (3) cells (3.6-5.8 11m diameter) with irregularly shaped nuclei and marginal condensed chromatin in a myxomatous matrix. Some mitotic figures, binucleate cells, and multinucleate giant cells of up to 50 11m in length were also found. Flow cytometry of propidium iodide-stained cells yielded different histograms for the normal skin and the skin (primarily epidermis) and fibrous dermis of the tumor, indicating DNA heterogeneity in the dermal portion of the tumor. The ploidy indices for the dermal cells were 1.91 and 0.78, as compared to normal cells.

• IMMUNE NETWORK
• /
• v.3 no.1
• /
• pp.38-46
• /
• 2003

Background: Platelet-activating factor (PAF) induces nuclear factor $(NF)-{\kappa}B$ activation and angiogenesis and increases tumor growth and pulmonary tumor metastasis in vivo. The role of $NF-{\kappa}B$ activation in PAF-induced angiogenesis in a mouse model of Matrigel implantation, and in PAF-mediated pulmonary tumor metastasis were investigated. Methods: Angiogenesis using Matrigel and experimental pulmonary tumor metastasis were tested in a mouse model. Electrophoretic mobility shift assay was done for the assessment of $NF-{\kappa}B$ translocation to the nucleus. Expression of angiogenic factors, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\alpha}$, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were tested by RT-PCR and ELISA. Results: PAF induced a dose- and time-dependent angiogenic response. PAF-induced angiogenesis was significantly blocked by PAF antagonist, CV6209, and inhibitors of $NF-{\kappa}B$ expression or action, including antisense oligonucleotides to p65 subunit of $NF-{\kappa}B$ (p65 AS) and antioxidants such as ${\alpha}$-tocopherol and N-acetyl-L-cysteine. In vitro, PAF activated the transcription factor, $NF-{\kappa}B$ and induced mRNA expression of $TNF-{\alpha}$, $IL-1{\alpha}$, bFGF, VEGF, and its receptor, KDR. The PAF-induced expression of the above mentioned factors was inhibited by p65 AS or antioxidants. Also, protein synthesis of VEGF was increased by PAF and inhibited by p65 AS or antioxidants. The angiogenic effect of PAF was blocked when anti-VEGF antibodies was treated or antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF was co-administrated, but not by antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF each alone. PAF-augmented pulmonary tumor metastasis was inhibited by p65 AS or antioxidants. Conclusion: These data indicate that PAF increases angiogenesis and pulmonary tumor metastasis through $NF-{\kappa}B$ activation and expression of $NF-{\kappa}B$-dependent angiogenic factors.

• Journal of Microbiology and Biotechnology
• /
• v.17 no.11
• /
• pp.1856-1861
• /
• 2007

Physiological cell conditions such as glucose deprivation and hypoxia play roles in the development of drug resistance in solid tumors. These tumor-specific conditions cause decreased expression of DNA topoisomerase $II{\alpha}$, rendering cells resistant to topo II target drugs such as etoposide. Thus, targeting tumor-specific conditions such as a low glucose environment may be a novel strategy in the development of anticancer drugs. On this basis, we established a novel screening program for anticancer agents with preferential cytotoxic activity in cancer cells under glucose-deprived conditions. We recently isolated an active compound, AA-98, from Streptomyces sp. AA030098 that can prevent stress-induced etoposide resistance in vitro. Furthermore, LC-MS and various NMR spectroscopic methods identified AA-98 as mithramycin, which belongs to the aureolic acid group of antitumor compounds. We found that mithramycin prevents the etoposide resistance that is induced by glucose deprivation. The etoposide-chemosensitive action of mithramycin was just dependent on strict low glucose conditions, and resulted in the selective cell death of etoposide-resistant HT-29 human colon cancer cells.

• BMB Reports
• /
• v.55 no.1
• /
• pp.48-56
• /
• 2022

Small extracellular vesicles (sEVs) secreted by most cells carry bioactive macromolecules including proteins, lipids, and nucleic acids for intercellular communication. Given that some immune cell-derived sEVs exhibit anti-cancer properties, these sEVs have received scientific attention for the development of novel anti-cancer immunotherapeutic agents. In this paper, we reviewed the latest advances concerning the biological roles of immune cell-derived sEVs for cancer therapy. sEVs derived from immune cells including dendritic cells (DCs), T cells, natural-killer (NK) cells, and macrophages are good candidates for sEV-based cancer therapy. Besides their role of cancer vaccines, DC-shed sEVs activated cytotoxic lymphocytes and killed tumor cells. sEVs isolated from NK cells and chimeric antigen receptor (CAR) T cells exhibited cytotoxicity against cancer cells. sEVs derived from CD8⁺ T and CD4⁺ T cells inhibited cancer-associated cells in tumor microenvironment (TME) and activated B cells, respectively. M1-macrophage-derived sEVs induced M2 to M1 repolarization and also created a pro-inflammatory environment. Hence, these sEVs, via mono or combination therapy, could be considered in the treatment of cancer patients in the future. In addition, sEVs derived from cytokine-stimulated immune cells or sEV engineering could improve their anti-tumor potency.

• BMB Reports
• /
• v.56 no.5
• /
• pp.287-295
• /
• 2023

The tumor microenvironment (TME) is a complex system composed of many cell types and an extracellular matrix (ECM). During tumorigenesis, cancer cells constantly interact with cellular components, biochemical cues, and the ECM in the TME, all of which make the environment favorable for cancer growth. Emerging evidence has revealed the importance of substrate elasticity and biomechanical forces in tumor progression and metastasis. However, the mechanisms underlying the cell response to mechanical signals-such as extrinsic mechanical forces and forces generated within the TME-are still relatively unknown. Moreover, having a deeper understanding of the mechanisms by which cancer cells sense mechanical forces and transmit signals to the cytoplasm would substantially help develop effective strategies for cancer treatment. This review provides an overview of biomechanical forces in the TME and the intracellular signaling pathways activated by mechanical cues as well as highlights the role of mechanotransductive pathways through mechanosensors that detect the altering biomechanical forces in the TME.

• Biomedical Science Letters
• /
• v.20 no.3
• /
• pp.103-110
• /
• 2014

Matrix metalloproteinases (MMPs), also called matrixins, function in the extracellular environment of cells and degrade both matrix and non-matrix proteins. They are multidomain proteins and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs). The uncontrolled regulation of MMPs is involved in various pathologic processes, such as tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Especially, matrix metalloproteinase-9 (MMP-9) is one of the metastasis-accelerating genes involved in metastasis of various types of human cancers. Here, we review the member of MMP family and discusses their domain structure and function, enzyme activation, the mechanism of inhibition by TIMPs. In particular, we focus the role of MMP-9 in relation to cancer metastasis.

• The Korean Journal of Cytopathology
• /
• v.19 no.2
• /
• pp.72-85
• /
• 2008

Cytologic examination of the body cavity fluid is very important because the specimens represent a significant percentage of nongynecologic samples and this cytologic examination may be the first, best or only chance for making the diagnosis of an underlying malignancy. The purposes of body cavity fluid examination are to correctly identify cancer cells and if possible, to identify the tumor types and primary sites when presented with unknown primary tumor sites. The most important basic differential diagnosis is that of benign and reactive disease vs malignant disease. Reactive mesothelial cells are a consistent population in body cavity fluid, and these are the most versatile cells in the body. Due to the specific environment of the body cavity, the exfoliated reactive mesothelial cells may show significant morphologic overlap with the morphology of cancer cells. With a focus on the differential points between reactive mesothelial cells and metastatic adenocarcinoma cells, the practical diagnostic approaches, the diagnostic clues and the pitfalls to achieve a correct diagnosis are presented in this review.

• Mass Spectrometry Letters
• /
• v.10 no.3
• /
• pp.71-78
• /
• 2019

For several decades, cancer has been the primary cause of mortality worldwide. New diagnosis and regimens have been developed to improve the chemotherapeutic efficacy and the quality of life of the patients. However, cancer tissues are complex and difficult to assess. Understanding the various properties of the tumor and its environment is crucial for cancer and pharmaceutical research. Several analytical techniques have been providing new insights into cancer research. Recently, matrix-assisted laser desorption ionization (MALDI)-mass spectrometry imaging (MSI), an advanced analytical technique, has been applied to translational research. Proteomic and lipidomic profiling obtained by MALDI-MSI has been critical for biomarker discovery and for monitoring heterogenous tumor tissues. In this review, we discuss technical approaches, benefits and recent applications of MALDI-MSI as a valuable tool in cancer research, namely for diagnosis, therapy, prognosis.